Repair of DNA damage is crucial to prevent accumulation of mutations that can cause human disease, such as cancer. Our lab studies how double-strand breaks in the DNA, one of the most lethal types of DNA lesions, are repaired. Many proteins are important for DNA repair including Sgs1, a protein that when mutated in human cells leads to many devastating diseases (i.e. Bloom, Werner, Rothmund-Thomson syndromes), which are all fundamentally characterized by cancer predisposition/premature aging. Sgs1 genetically interacts with a group of proteins collectively called the Shu complex. Although Sgs1 has been extensively analyzed, the molecular mechanism of how it functions to repair DNA damage and its relationship to the Shu complex has remained elusive, largely because its deletion leads to many pleiotropic phenotypes. Our lab uses cell biological, molecular, and genetic approaches to study the role of double-strand break repair proteins, such as Sgs1 and the Shu complex, in response to DNA damage. By understanding the mechanism of double-strand break repair and the role of DNA repair proteins in this process, we will uncover mechanisms of tumorigenesis and cancer progression. We will then use this knowledge to aid in diagnosis/prognosis of different types of cancers and to find novel therapeutic targets.